Abstract
BACKGROUNDS
Prognosis of relapsed primary central nervous system lymphoma (rPCNSL) is poor ranging between 2.2 and 16 months, and the optimal treatment strategy has not been established. Tirabrutinib is a second generation Bruton’s tyrosine kinase (BTK) inhibitor, approved by the Japanese Pharmaceutical and Medical Devices Agency (PMDA) for relapsed and refractory (r/r) PCNSL in March 2020. While an overall response rate (ORR) of 64% and progression-free survival (PFS) of 2.9 months was reported in a phase 1/2 study, the real-world treatment results of rPCNSL treated with tirabrutinib have not been investigated yet.
METHODS
Treatment results of rPCNSL patients treated with tirabrutinib at the author’s institution including response rate, PFS, overall survival (OS), and toxicity profiles were retrospectively analyzed.
RESULTS
Eleven patients were identified (median age: 73 [range: 50-83], median PFS: 70 [range: 40-90]). Response was CR in four (36.4%), PR in five (45.4%), PD in two (18.2%) patients, providing with an ORR of 81.8%. At a median follow up of 25.7 months, relapse was observed in seven patients (63.6%), and median PFS was 3.0 months. Durable remission of more than six months was obtained in four patients (36.4%). As for toxicities, six patients (54.5%) had skin-related disorders, which lead to tirabrutinib interruption in two (18.2%), dose reduction in three (27.3%), and discontinuation in two patients (18.2%). Grade 3/4 hematological toxicities were grade 4 neutropenia in one, and grade 3 lymphopenia in five patients (45.4%). No deaths have been observed.
DISCUSSION
Tirabrutinib monotherapy achieved a high response rate in rPCNSL, while skin-related disorders appeared to be the major obstacle leading to treatment interruption or discontinuation. Overall median PFS was in line with the phase 1/2 study. A subset of patients achieved durable remission, suggesting its strong benefit in certain patients. Further investigation of predictive biomarkers for response to tirabrutinib is warranted.